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In Vivo and In Vitro Pharmacokinetic Studies of a Dual Topoisomerase I/II Inhibitor.

Due to high mortality rates, new and more effective drugs are urgently needed in cancer therapy. The novel dual topoisomerase inhibitor P8-D6, a dimethylaminoethyl-substituted pyridophenanthroline, showed in vitro impressive induction of apoptosis in tumors such as ovarian cancer or multiple myeloma compared to the current standard therapy. The purpose of this study was to investigate its in vitro and in vivo pharmacokinetics and to discover further potential drug candidates. Samples of plasma, various tissues, urine, feces, and cell culture supernatants were examined by HPLC. In addition, the

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… Afterward, a piece of 150–300 mg was cut off with a scalpel, divided into small parts, and homogenized with 1500 μL of ice-cold buffer (containing 0.25 M saccharose, 50 mM KCl, 1 mM EDTA, 10 mM potassium dihydrogen phosphate, and 1 mM dithiothreitol at pH 7.4) for about 5 min using a Potter S homogenizer …

Research advances in peptide‒drug conjugates.

Peptide‒drug conjugates (PDCs) are drug delivery systems consisting of a drug covalently coupled to a multifunctional peptide via a cleavable linker. As an emerging prodrug strategy, PDCs not only preserve the function and bioactivity of the peptides but also release the drugs responsively with the cleavable property of the linkers. Given the ability to significantly improve the circulation stability and targeting of drugs in vivo and reduce the toxic side effects of drugs, PDCs have already been extensively applied in drug delivery. Herein, we review the types and mechanisms of peptides, link

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… There was a significant acceleration of DM1 release from RSSD@NPs after the addition of the reducing agent dithiothreitol (DTT), increasing from 27.0% to 78.6% within 48 h, as indicated by the drug release curves ( Fig. 8 B). …

Brain intratumoural astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice.

BackgroundGlioblastoma (GB), the most aggressive brain cancer, remains a critical clinical challenge due to its resistance to conventional treatments. Here, we introduce a locoregional targeted-α-therapy (TAT) with the rat monoclonal antibody 9E7.4 targeting murine syndecan-1 (SDC1) coupled to the α-emitter radionuclide astatine-211 (211At-9E7.4).MethodsWe orthotopically transplanted 50,000 GL261 cells of murine GB into the right striatum of syngeneic female C57BL/6JRj mice using stereotaxis. After MRI validation of tumour presence at day 11, TAT was injected at the same coordinates. Biodistri

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… distillation protocol adapted from the procedure previously reported by Lindegren et al. 34 [ 211 At]NaAt was then obtained by reducing to dryness the chloroformic astatine solution under a gentle stream of nitrogen to obtain dry astatine, followed by dissolution in an appropriate volume of 10 mg/mL dithiothreitol …

Direct Endoplasmic Reticulum Targeting by the Selective Alkylphospholipid Analog and Antitumor Ether Lipid Edelfosine as a Therapeutic Approach in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC), the most common malignancy of the pancreas, shows a dismal and grim overall prognosis and survival rate, which have remained virtually unchanged for over half a century. PDAC is the most lethal of all cancers, with the highest mortality-to-incidence ratio. PDAC responds poorly to current therapies and remains an incurable malignancy. Therefore, novel therapeutic targets and drugs are urgently needed for pancreatic cancer treatment. Selective induction of apoptosis in cancer cells is an appealing approach in cancer therapy. Apoptotic cell death is highly

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… Preincubation of BxPC-3 pancreatic cells with dithiothreitol (DTT)—a well-known ER stress and UPR inducer—did not lead to a statistically significant reduction in edelfosine-induced apoptosis [ 132 ], further supporting the notion that persistent edelfosine-induced ER stress overrides protective UPR …

Progress of Cancer Nanotechnology as Diagnostics, Therapeutics, and Theranostics Nanomedicine: Preclinical Promise and Translational Challenges.

Early detection, right therapeutic intervention, and simultaneous effectiveness mapping are considered the critical factors in successful cancer therapy. Nevertheless, these factors experience the limitations of conventional cancer diagnostics and therapeutics delivery approaches. Along with providing the targeted therapeutics delivery, advances in nanomedicines have allowed the combination of therapy and diagnostics in a single system (called cancer theranostics). This paper discusses the progress in the pre-clinical and clinical development of therapeutics, diagnostics, and theranostics canc

Antibody-based drug delivery systems for cancer therapy: Mechanisms, challenges, and prospects.

In recent years, antibody-based cancer therapy has emerged as one of the efficient therapeutic strategies, such as immune checkpoint inhibitors (ICIs), angiogenesis inhibitors, antibody-drug conjugates (ADCs), multi-specific antibodies, and chimeric antigen receptor T (CAR-T) cells, among others. To date, various drug delivery platforms have been developed to improve the bioavailability, delivery convenience, and reduced toxicity towards increased therapeutic efficacy of antibodies. Herein, we emphasize the clinical manifestations of various antibody-based tumor therapies, highlighting their m

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… In their design, antibodies were treated with immunoglobulin-degrading enzyme to cleave IgG molecules below the hinge region, and then reduced by dithiothreitol to obtain sulfhydryl group, which could be chemically coupled with the maleimide group on the surface of PLGA NPs ( Figure 7 A ). …

Theranostics - a sure cure for cancer after 100 years?

Cancer has remained a formidable challenge in medicine and has claimed an enormous number of lives worldwide. Theranostics, combining diagnostic methods with personalized therapeutic approaches, shows huge potential to advance the battle against cancer. This review aims to provide an overview of theranostics in oncology: exploring its history, current advances, challenges, and prospects. We present the fundamental evolution of theranostics from radiotherapeutics, cellular therapeutics, and nanotherapeutics, showcasing critical milestones in the last decade. From the early concept of targeted d

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… For example, Palange et al. designed a biodegradable hydrogel microparticle by cross-linking PEG with hydrolyzable 1,4-dithiothreitol, which had been loaded with 200 nm NPs carrying therapeutic and imaging agents (Figure 10 A) 130 . …

Increased Indoleamine 2, 3-Dioxygenase expression modulates Th1/Th17/Th22 and Treg pathway in humans with Helicobacter Pylori-Infected gastric mucosa.

Introduction and purposeIndoleamine 2, 3- dioxygenase (IDO) plays an importantrole in immunosuppressive pathway, as inhibits responsesof T cells and promotes immune tolerance. Host responsetoHelicobacter pylori (H. pylori) is involved in the infection persistenceand it is also associatedwith different clinical outcomes. The aim of this study was to investigate the role of IDO in H. pylori-infected patients with gastritis diseases and peptic ulcer diseases (PUD) through the assessment of the relationship among IDO protein expression and the numbers of T helper (Th)-1, Th17, Th22, and T regulato

"Bioinspired" Membrane-Coated Nanosystems in Cancer Theranostics: A Comprehensive Review.

Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core sel

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… The technique involves the use of a gel matrix consisting of polyacrylamide, along with a detergent (SDS) and a reducing agent (such as β-mercaptoethanol or dithiothreitol) that denatures and imparts a uniform negative charge to the proteins. …

Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.

A prodrug is a molecule that lacks pharmacological activity, but upon enzymatic bioactivation, it can generate a therapeutically active molecule. The primary reason behind the design of a prodrug is to help circumvent challenges associated with the physicochemical properties of a drug molecule, such as solubility, absorption, distribution, and instability. Chemotherapy has been at the forefront of cancer treatment for over 70 years due to its ability to target rapidly proliferating tumor cells. However, a major concern with conventional chemotherapy is the lack of selectivity and its associate

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… Furumai et al. demonstrated that the reduced form of romidepsin was active, as evidenced by the enhanced IC 50 for HDAC inhibition by adding reducing agents such as dithiothreitol [ 196 , 197 ]. …

Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination.

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much highe

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… A simple, non-selective reduction is rather improbable since glutathione, L-cysteine, or dithiothreitol are inactive. …

"Smart" drug delivery: A window to future of translational medicine.

Chemotherapy is the mainstay of cancer treatment today. Chemotherapeutic drugs are non-selective and can harm both cancer and healthy cells, causing a variety of adverse effects such as lack of specificity, cytotoxicity, short half-life, poor solubility, multidrug resistance, and acquiring cancer stem-like characteristics. There is a paradigm shift in drug delivery systems (DDS) with the advent of smarter ways of targeted cancer treatment. Smart Drug Delivery Systems (SDDSs) are stimuli responsive and can be modified in chemical structure in response to light, pH, redox, magnetic fields, and e

Novel Combinatorial Approaches to Tackle the Immunosuppressive Microenvironment of Prostate Cancer.

Prostate cancer (PCa) is the second-most common cancer in men worldwide and treatment options for patients with advanced or aggressive prostate cancer or recurrent disease continue to be of limited success and are rarely curative. Despite immune checkpoint blockade (ICB) efficacy in some melanoma, lung, kidney and breast cancers, immunotherapy efforts have been remarkably unsuccessful in PCa. One hypothesis behind this lack of efficacy is the generation of a distinctly immunosuppressive prostate tumor microenvironment (TME) by regulatory T cells, MDSCs, and type 2 macrophages which have been i

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… Notably, addition of exogenous ER stress-inducers thapsigargin or dithiothreitol effectively converts neutrophils into LOX-1+ PMN-MDSCs [ 92 ]. …

Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks.

Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host's immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional,

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… The protein molecules were reduced using succinimidyl 4-(p-maleidophenyl butyrate) (SMPB) or dithiothreitol (DTT) for binding to the phospholipid heads external to the liposome, similar to such methods used for antibodies [ 104 ]. 3.3.4. …

Применение искусственного интеллекта в перипостетической суставной инфекции.

Перипростетическая суставная инфекция (ПСО) представляет собой one Из наиболее разрушительных осложнений, вызванных общей совместной артропластикой, часто требующих дополнительных операций и антимикробной терапии, и потенциально ведущих к инвалидности. Это значительно увеличивает нагрузку как на пациентов, так и на систему здравоохранения. С учетом значительных страданий, причиняемых ПСО, его профилактика и лечение уже давно являются ключевыми факторами, вызывающими озабоченность. Вместе с тем сохраняются проблемы, связанные с точной оценкой индивидуального риска, предотвращением инфекции, сов

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… This includes techniques like bead milling, mechanical grinding, and dithiothreitol (DTT) pre-treatment of periprosthetic tissues [157] , [158] , [159] , [160] , [161] , as well as ultrasonic treatment of SF, periprosthetic tissues, and prosthetic components, and employing various identification methods …

Tumor-derived systems as novel biomedical tools-turning the enemy into an ally.

Cancer is a complex illness that presents significant challenges in its understanding and treatment. The classic definition, "a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body," fails to convey the intricate interaction between the many entities involved in cancer. Recent advancements in the field of cancer research have shed light on the role played by individual cancer cells and the tumor microenvironment as a whole in tumor development and progression. This breakthrough enables the utilization of the tumor and its components as biological

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… Following isolation, the exosomes are liberated from the chip by cleaving the disulfide bond with dithiothreitol (DTT). The authors systematically fine-tuned the concentration and flow rate of DTT release to optimize the recovered exosome yield and purity. …

Poster Abstracts

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2020 ACVIM Forum On Demand Research Abstract Program.

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Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.

Protein folding is a fundamental process ensuring that polypeptide chains acquire the correct three-dimensional structures required for biological function. This complex journey from nascent polypeptides to mature proteins is tightly regulated by the cellular proteostasis network-an integrated system of molecular chaperones, folding enzymes, and degradation machineries. Disruptions in this network lead to dysproteostasis, a pathological state implicated in a growing list of human diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. In this review, we provide a comp

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… CRYAB mutations, the D140N variant results in an altered tertiary structure, increased surface hydrophobicity, and increased heat-induced aggregation, with a dominant negative effect on its wild-type counterpart. 239 In addition, while wild-type CRYAB exhibited intact chaperone activity by inhibiting dithiothreitol …

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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